Quantification of Global DNA Methylation in Canine Mammary Gland Tumors via Immunostaining of 5-Methylcytosine: Histopathological and Clinical Correlations

Biondi, Luiz Roberto; Tedardi, Marcello Vannucci; Gentile, Luciana Boffoni; Chamas, Patricia Pereira Costa; Dagli, M.L.

doi:10.3389/fvets.2021.628241

Cited by 7 publications

(6 citation statements)

References 31 publications

(38 reference statements)

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“…In contrast (18,19,30), demonstrated that the most aggressive tumor subtypes have shown predominant weakly stained nuclei that presumably revealed global DNA hypomethylation. Unfortunately, in this study, we could not evaluate the normal methylation pattern of canine mucosal melanocytes, since these cells are roughly seen in histological sections of oral mucosa in clinically healthy dogs.…”

Section: Discussionmentioning

confidence: 91%

“…The OMM slides were analyzed in an image analysis system to quantify strong, weak, or negative nuclei (at least 500 per case). The same quantification approach was used in other studies ( 18 , 19 , 30 ). The results of these quantifications showed that both melanotic and amelanotic OMMs presented higher percentages of weakly stained and negative 5mC nuclei.…”

Section: Discussionmentioning

confidence: 99%

“…Based on our previous studies using anti-5-methylcytosine (5mC) immunostaining, global DNA methylation patterns was found to differ in mast cell tumor grades ( 18 ): grade 3, high-grade mast cell tumors, which present worse prognosis, showed predominant weak immunostaining for 5mC. Moreover, canine mammary cancers ( 19 ) were identified to develop a higher aggressiveness in hypomethylated (predominantly 5mC-weakly immunostained) tumors.…”

Section: Introductionmentioning

confidence: 99%

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Quantification of Global DNA Methylation in Canine Melanotic and Amelanotic Oral Mucosal Melanomas and Peripheral Blood Leukocytes From the Same Patients With OMM: First Study

et al. 2021

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Oral mucosal melanomas (OMMs) are aggressive and resistant cancers of high importance in veterinary oncology. Amelanotic OMM produces comparatively less melanin and is considered to be more aggressive than melanotic OMM. Global DNA methylation profiles with hypomethylated or hypermethylated patterns have both been associated with aggressive neoplasms; however, global DNA hypomethylation seems to correlate to higher aggressiveness. Accordingly, global DNA methylation in peripheral blood leukocytes has been investigated to understand the role of systemic or environmental factors in cancer development. This study aimed to quantify global DNA methylation in canine melanotic and amelanotic OMM samples and in the peripheral blood leukocytes of the same dogs. Tumor tissue samples were collected from 38 dogs, of which 19 were melanotic and 19 were amelanotic OMM. These were submitted to immunohistochemistry (IHC) with anti-5-methylcytosine (5mC) and anti-Ki67 primary antibodies. Ki67- and 5mC-positive nuclei were manually scored with the help of an image analysis system. Peripheral blood samples were collected from 18 among the 38 OMM-bearing dogs and from 7 additional healthy control dogs. Peripheral blood leukocytes were isolated from the 25 dogs, and DNA was extracted and analyzed by high-performance liquid chromatography (HPLC) for global DNA methylation. The pattern of global DNA methylation in both canine melanotic and amelanotic OMM indicated higher percentages of weakly or negatively stained nuclei in most of the OMM cells, presuming predominant global DNA hypomethylation. In addition, Ki67 counts in amelanotic OMM were significantly higher than those in melanotic OMM (p < 0.001). Global DNA methylation different immunostaining patterns (strong, weak or negative) correlated with Ki67 scores. Global DNA methylation in circulating leukocytes did not differ between the 9 melanotic and 9 amelanotic OMM or between the 18 OMM-bearing dogs and the 7 healthy dogs. This study provides new information on canine melanotic and amelanotic OMM based on global DNA methylation and cell proliferation.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantification of Global DNA Methylation in Canine Melanotic and Amelanotic Oral Mucosal Melanomas and Peripheral Blood Leukocytes From the Same Patients With OMM: First Study

et al. 2021

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“…In a broader analysis, Biondi et al (2021 ), who analyzed the global genome methylation pattern of canine mammary tumors by immunohistochemistry, described a lower hypermethylation pattern for malignant samples, which is associated with tumor recurrence. In the same way, in mammary tissues as well as in plasma, Lee et al (2019 ) observed a low methylation level in LINE-1, a retrotransposon, in benign and tumor samples when compared with healthy samples.…”

Section: Dna Methylationmentioning

confidence: 99%

Epigenetic alterations in canine mammary cancer

Borges

2022

Genet. Mol. Biol.

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In dogs, mammary cancer is the most common tumor type, especially in unspayed females. As in humans, this type of cancer has spontaneous development and is influenced by several risk factors, such as age and hormonal exposure in addition to genetic and epigenetic factors. Epigenetic mechanisms are responsible for gene expression modulation without alterations in the DNA sequence and include but are not limited to DNA methylation, histone modifications, and noncoding RNAs. Epigenetic patterns are known to influence a variety of biological mechanisms, such as cellular differentiation and development, and dysregulations of those patterns may result in several diseases, such as cancer. In this respect, this review summarizes the main findings concerning epigenetic alterations in canine mammary cancer, their relationship with the carcinogenic process, and their use as diagnostic and prognostic markers.

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“…In the conditions of multiple tumours of the mammary gland, average and overall sizes of malignant tumours are related to non-relapse life (Pecile et al, 2021). The level of methylation of DNA chains (evaluated by 5-methylcytosine) in mammary tumours correlates with size and prognosis for patients (Biondi et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Prognostic markers of canine mammary tumours: Retrospective study of 142 cases

Kovalenko

Bilyi

Skliarov

et al. 2021

Regul. Mech. Biosyst.

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Due to relevance of the problem, prediction of biological behaviour of neoplasias in mammary glands of dogs requires using contemporary approaches to the study, first of all, of ways of dissemination of tumour cells. One of them is studying the mechanisms of migration of cancer cells out of the neoplasm tissues with further dissemination and development of metastatic sites in the regional lymphatic nodes and remote tissues. We studied the survival period of bitches with tumours of the mammary glands following regional or unilateral mastectomy. Among malignant mammary tumours in bitches, the most often diagnosed were single tumours (57.5%), which histologically were classified to carcinomas – ductal (26.9%) and mixed type (21.9%). Probability of intratumoral invasion to blood vessels equaled 12.0%, to lymph vessels – 7.8%, lymph nodes – 12.8%. It depends on the histological type of the tumour, the most aggressive potentially being сomedocarcinoma, tubulopapillary carcinoma and ductal carcinoma. Parameters of life expectancy and survival level after mastectomy depend on clinical stage of the disease (increase in the stage from the first to the third was characterized by decrease from 12.8 ± 9.5 to 9.4 ± 7.8 months), presence of angio/lymphatic invasions, presence of angiolymphatic invasion, but had no correlation with the size of the tumours. An important predictor of tumour-related death of dogs suffering neoplasias of the mammary glands is index vet-NPI, which has significant correlation with the clinical stage according to Owen and median survival. In particular, median survival in patients with the index lower than 4 exceeded the corresponding values in dogs with the index above 4 by 1.3 times. A promising direction of further research would be studying biological mechanisms of development of tumour emboli in the blood and lymph vessels, metastatic sites in lymph nodes, and also determining their role in pathogenesis of canine mammary tumours.

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Quantification of Global DNA Methylation in Canine Mammary Gland Tumors via Immunostaining of 5-Methylcytosine: Histopathological and Clinical Correlations

Cited by 7 publications

References 31 publications

Quantification of Global DNA Methylation in Canine Melanotic and Amelanotic Oral Mucosal Melanomas and Peripheral Blood Leukocytes From the Same Patients With OMM: First Study

Quantification of Global DNA Methylation in Canine Melanotic and Amelanotic Oral Mucosal Melanomas and Peripheral Blood Leukocytes From the Same Patients With OMM: First Study

Epigenetic alterations in canine mammary cancer

Prognostic markers of canine mammary tumours: Retrospective study of 142 cases

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